表现为早期隐球菌性脑膜炎且脑脊液分析阴性的症状性隐球菌抗原血症。
Symptomatic Cryptococcal Antigenemia Presenting as Early Cryptococcal Meningitis With Negative Cerebral Spinal Fluid Analysis.
机构信息
Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis.
出版信息
Clin Infect Dis. 2019 May 30;68(12):2094-2098. doi: 10.1093/cid/ciy817.
BACKGROUND
Individuals with cryptococcal antigenemia are at high risk of developing cryptococcal meningitis if untreated. The progression and timing from asymptomatic infection to cryptococcal meningitis is unclear. We describe a subpopulation of individuals with neurologic symptomatic cryptococcal antigenemia but negative cerebral spinal fluid (CSF) studies.
METHODS
We evaluated 1201 human immunodeficiency virus-seropositive individuals hospitalized with suspected meningitis in Kampala and Mbarara, Uganda. Baseline characteristics and clinical outcomes of participants with neurologic-symptomatic cryptococcal antigenemia and negative CSF cryptococcal antigen (CrAg) were compared to participants with confirmed CSF CrAg+ cryptococcal meningitis. Additional CSF testing included microscopy, fungal culture, bacterial culture, tuberculosis culture, multiplex FilmArray polymerase chain reaction (PCR; Biofire), and Xpert MTB/Rif.
RESULTS
We found 56% (671/1201) of participants had confirmed CSF CrAg+ cryptococcal meningitis and 4% (54/1201) had neurologic symptomatic cryptococcal antigenemia with negative CSF CrAg. Of those with negative CSF CrAg, 9% (5/54) had Cryptococcus isolated on CSF culture (n = 3) or PCR (n = 2) and 11% (6/54) had confirmed tuberculous meningitis. CSF CrAg-negative patients had lower proportions with CSF pleocytosis (16% vs 26% with ≥5 white cells/μL) and CSF opening pressure >200 mmH2O (16% vs 71%) compared with CSF CrAg-positive patients. No cases of bacterial or viral meningitis were detected by CSF PCR or culture. In-hospital mortality was similar between symptomatic cryptococcal antigenemia (32%) and cryptococcal meningitis (31%; P = .91).
CONCLUSIONS
Cryptococcal antigenemia with meningitis symptoms was the third most common meningitis etiology. We postulate this is early cryptococcal meningoencephalitis. Fluconazole monotherapy was suboptimal despite Cryptococcus-negative CSF. Further studies are warranted to understand the clinical course and optimal management of this distinct entity.
CLINICAL TRIALS REGISTRATION
NCT01802385.
背景
未经治疗的隐球菌抗原血症患者有发展为隐球菌性脑膜炎的高风险。从无症状感染到隐球菌性脑膜炎的进展和时间尚不清楚。我们描述了一组具有神经症状性隐球菌抗原血症但中枢神经系统（CSF）研究阴性的人群。
方法
我们评估了在乌干达坎帕拉和姆巴拉拉因疑似脑膜炎住院的 1201 名人类免疫缺陷病毒（HIV）阳性个体。比较了具有神经症状性隐球菌抗原血症和阴性 CSF 隐球菌抗原（CrAg）的参与者与确诊 CSF CrAg+隐球菌性脑膜炎的参与者的基线特征和临床结局。CSF 的其他检测包括显微镜检查、真菌培养、细菌培养、结核分枝杆菌培养、多重 FilmArray 聚合酶链反应（PCR；Biofire）和 Xpert MTB/Rif。
结果
我们发现 56%（1201 例中的 671 例）的参与者有确诊的 CSF CrAg+隐球菌性脑膜炎，4%（1201 例中的 54 例）有神经症状性隐球菌抗原血症和阴性 CSF CrAg。在阴性 CSF CrAg 的患者中，9%（5/54）在 CSF 培养（n=3）或 PCR（n=2）中分离出隐球菌，11%（6/54）有确诊的结核性脑膜炎。CSF CrAg 阴性患者的 CSF 白细胞增多（≥5 个白细胞/μL）比例较低（16% vs 26%），CSF 开放压>200mmH2O 比例较低（16% vs 71%），与 CSF CrAg 阳性患者相比。通过 CSF PCR 或培养未检测到细菌性或病毒性脑膜炎。症状性隐球菌抗原血症（32%）和隐球菌性脑膜炎（31%；P=.91）的院内死亡率相似。
结论
有脑膜炎症状的隐球菌抗原血症是第三大常见的脑膜炎病因。我们推测这是早期的隐球菌脑膜脑炎。尽管 CSF 为阴性，但氟康唑单药治疗效果不佳。需要进一步研究以了解这种独特实体的临床过程和最佳治疗方法。
临床试验注册
NCT01802385。
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